Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (S,R)-{2-[2-(2-bromo-imidazo[2,1-b]thiazol-6-ylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl}-carbamic acid tert-butyl ester

HRID 1811665Notes

Reaction equation

HRID 1811665 reaction equation
Cl.[Br:2][C:3]1[S:7][C:6]2=[N:8][C:9]([NH2:11])=[CH:10][N:5]2[CH:4]=1.[C:12]([O:16][C:17]([NH:19][C@H:20]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@H:24]1[C:28](O)=[O:29])=[O:22])=[O:18])([CH3:15])([CH3:14])[CH3:13].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:12]([O:16][C:17](=[O:18])[NH:19][C@@H:20]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:21]([N:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[C:28](=[O:29])[NH:11][C:9]1[N:8]=[C:6]2[N:5]([CH:10]=1)[CH:4]=[C:3]([Br:2])[S:7]2)=[O:22])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10089106(S,R)-1-(2-tert-butoxycarbonylamino-2-phenylacetyl)-pyrrolidine-2-carboxylic acidHCID 672405282-Bromo-imidazo[2,1-b]thiazol-6-ylamine hydrochloride

Product 1

HCID 86654641(S,R)-{2-[2-(2-bromo-imidazo[2,1-b]thiazol-6-ylcarbamoyl)-pyrrolidin-1-yl]-2-oxo-1-phenyl-ethyl}-carbamic acid tert-butyl esterYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of compound 11 (0.137 mmol), compound 3a (0.206 mmol), and HATU (0.206 mmol) in dimethylformamide (1.5 mL) was added TEA (0.55 mmol) dropwise. The reaction mixture was stirred at 40° C. for 4 hrs. The solvent was removed under reduced pressure and the residue dissolved in a mixture of dichloromethane/methanol (9/1). This mixture was passed through a SCX-2 column and the column was washed three times with the same eluent. The filtrate was concentrated and the residue was purified by chromatography on a silica gel column to give compound 12a as a yellow orange solid in 18% yield. MS (ESI, EI+) m/z=548.24-550.20 (MH+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in a mixture of dichloromethane/methanol (9/1)
  3. washthe column was washed three times with the same eluent
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-5c8ec60bddf34e5ca00606c59726545d
Source dataset
uspto-grants-2013_01
Patent number
US08362068B2

Reaction notes

Loading…